SynthesisClinical pharmacokinetics2022
Clinical Pharmacokinetic Monitoring of Free Valproic Acid Levels: A Systematic Review.
Synthesis in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- Personalized prediction of initial valproic acid dose in children with epilepsy using machine learning techniques.International journal of clinical pharmacy · 2026Article
- Determinants and Machine Learning Prediction of Subtherapeutic Sodium Valproate Concentrations in Epilepsy Management in Xinjiang, China.European journal of drug metabolism and pharmacokinetics · 2026Article
- Clinical Impact of Adjusted Valproic Acid Level in Patients with Hypoalbuminemia: A Single-Center Cohort Study.Journal of clinical pharmacology · 2026Article
- Article
- Physiologically Based Pharmacokinetic Modeling-Based Evaluation of Current Carbamazepine and Valproic Acid Dosing Guidelines for Pediatric Epilepsy Treatment.Paediatric drugs · 2025Article
- Prediction Trough Concentrations of Valproic Acid Among Chinese Adult Patients with Epilepsy Using Machine Learning Techniques.Pharmaceutical research · 2025Article
- Fixed parameters in the population pharmacokinetic modeling of valproic acid might not be suitable: external validation in Chinese adults with epilepsy or after neurosurgery.European journal of clinical pharmacology · 2024Article
- Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis.Psychopharmacology · 2024Article
- Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid.Journal of clinical laboratory analysis · 2024Article
- Evaluation ofPharmacogenomics and personalized medicine · 2024Article
- Unusual case of sodium valproate-induced hyperammonaemia encephalopathy.BMJ case reports · 2023Article
- Derivation and Validation of a New Equation for Estimating Free Valproate Concentration in Critically Ill Adult Patients.Critical care explorations · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCurrent guidelines recommend therapeutic drug monitoring as a critical component of valproic acid (VPA) therapy. Due to high protein binding, the active unbound (free) portion of VPA can be misrepresented by total VPA serum levels in certain clinical scenarios. Monitoring free VPA serum levels may be warranted when assessing the clinical response to VPA therapy.
objectivesThe aims were to conduct a systematic review to identify a therapeutic range for free VPA serum levels; to explore the correlation of free VPA serum levels with clinical toxicity and therapeutic benefit; and to examine predictors of discordance between free and total VPA levels.
methodsMedline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, BIOSIS Previews, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from the time of database inception to June 20, 2021. Randomized controlled trials and observational studies that evaluated any patient receiving VPA with free VPA level monitoring were included.
resultsOf 189 citations, we identified 27 relevant studies, which included 14 observational studies, two case series, and 11 case reports. Three studies provided a therapeutic range for free VPA levels between 20 and 410 μmol/L. Two studies suggested the occurrence of hyperammonemia and thrombocytopenia at free VPA serum levels above 60 µmol/L and 103.3 µmol/L, respectively. Two studies suggested an upper limit for neurotoxicity at free VPA serum levels of 70 µmol/L and 207.9 µmol/L. Hypoalbuminemia was identified as a predictor of therapeutic discordance.
conclusionsThis review demonstrates a paucity of data informing the clinical utility of free VPA serum levels. Further high-quality trials are needed to validate an optimal therapeutic range for free VPA levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.